As the major constituent cells of a renewing epidermis, keratinocytes are programmed to differentiate as they progress from the basal layer to the stratum corneum. In vitro, many of the changes characteristic of the differentiated phenotype can be induced by raising the extracellular Ca+2. This project is designed to examine whether membrane currents play a role in keratinocyte differentiation. Membrane currents of proliferative and differentiated keratinocytes will be defined and compared. Keratinocytes will be studied with a dual approach, correlating membrane currents with markers of differentiation. Agents which modify membrane currents will be tested for their ability to affect differentiation of cultured keratinocytes. This research may produce insight into the in vivo process of keratinocyte differentiation. Agents which modulate membrane currents and influence in vitro differentiation of cultured keratinocytes could be used to modulate growth and differentiation of keratinocytes in vivo. Information derived from this project could be applied to clinical problems such as wound healing.